The design, construction, assembly and testing of an external atmospheric pressure electrospray ionization source for an ion cyclotron resonance spectrometer is in progress. Ions formed at atmospheric pressure have been transmitted into the analyzer cell region, but further modifications are required in order to achieve efficient trapping. The completed electrospray system will be used to measure the molecular weights of proteins and DNA fragments. Derivatization chemistry suitable for optimizing the detection of acidic tryptophan metabolites by liquid chromatography-particle beam-negative chemical ionization mass spectrometry has been developed. Pentafluorobenzyl esters of tryptophan and six kynurenine metabolites could be separated and detected at the 25 pg level. A new derivatization reagent (1,1,1,7,7,7-hexafluoroheptanone) has been tested for use in forming cyclic ketals of glycols for improved detection in gas chromatography-mass spectrometry.